Isopropyl 2-ethylhexanoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

March 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Prediction is valid and reliable. QPRF not provided as model output but all the aspects used for QPRF purposes are well explained in the in silico study report.
This in silico study is considered to be an acceptable alternative to laboratory testing and of sufficient reliability (equivalent of Klimisch 2 where the prediction has been generated using valid QSARs with limited documentation provided as model output) to meet the testing requirements of REACH for the bacterial mutagenicity endpoint.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not applicable

Remarks:

Not applicable to QSAR prediction.

Principles of method if other than guideline:

The final QSAR prediction was derived taking into account the results from multiple QSAR tools listed in the report. In addition to the QSAR models, the substance was also screened through various Ames bacterial mutagenicity relevant profilers incorporated into structural alert tools. Finally, the KREATiS Study Director reached a conclusion on the potential of the substance for the Ames bacterial mutagenicity of isopropyl 2-ethylhexanoate based on the QSAR results and
structural alert information from the different tools.
Tools:
OECD QSAR Toolbox v4.2
Danish QSAR Database
VEGA v1.1.4
Toxtree v2.6.13
US EPA T.E.S.T v4.2.1

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl 2-ethylhexanoate

EC Number:

266-549-5

EC Name:

Isopropyl 2-ethylhexanoate

Cas Number:

67024-46-8

Molecular formula:

C11H22O2

IUPAC Name:

isopropyl 2-ethylhexanoate

Test material form:

liquid

Specific details on test material used for the study:

Not applicable to QSAR prediction.

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

not applicable

Test concentrations with justification for top dose:

Not applicable to QSAR prediction.

Vehicle / solvent:

Not applicable to QSAR prediction.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

not applicable

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: Not applicable to QSAR prediction.

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

not applicable

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

not applicable

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Test results 5

Key result

Species / strain:

E. coli WP2 uvr A

Additional information on results:

This in silico study summarises the final results reported with each tool and provides a
conclusion on Ames bacterial mutagenicity of the query substance based on a consensus approach taking into account all the reliable predictions from multiple QSARs and structural alert tools. The overall conclusion of this QSAR study is that isopropyl 2-ethylhexanoate is predicted not to be a bacterial mutagen, i.e. it is predicted to be Ames negative.

Tool Conclusion on Ames Mutagenicity
OECD QSAR Toolbox v4.2: Non-mutagenic
Danish QSAR Database: Non-mutagenic
VEGA v1.1.4: Non-mutagenic
Toxtree v2.6.13: Non-mutagenic
US EPA T.E.S.T v4.2.1: Non-mutagenic

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Applicant's summary and conclusion

Conclusions:

An in silico study on bacterial mutagenicity, based on a consensus approach taking into account reliable predictions from multiple QSARs and structural alert tools, concludes that isopropyl 2-ethylhexanoate is not a bacterial mutagen, i.e. it is predicted to be Ames negative.